Electrochemical controlled dispensing assembly and method

ABSTRACT

A pump assembly (20) employs electrochemistry to selectively control the delivery rate of a dispensing fluid (21) from a dispensing reservoir (24) by selectively controlling the flow rate of a driving fluid (19) from a driving reservoir (23) to a receiving reservoir (33). A partition (25), separating the driving reservoir from the receiving fluid reservoir, includes at least one aperture (28) which is opened or closed depending upon an electrical signal from a remote programming unit. Flow into the receiving reservoir deflects a barrier member to expel dispensing fluid from the dispensing reservoir. The dispensing fluid flow rate can be programmed to provide an appropriate steady or varying flow rate; user-initiated pulses of dispensing fluid can also be provided. A method of controlled infusion of an infusate employing electrochemistry is also provided.

CROSS REFERENCE TO RELATED APPLICATION

This application is a continuation-in-part of Ser. No. 08/012 876, filedFeb. 3, 1993 U.S. Pat. No. 5,290,240, the disclosure of which isincorporated by reference.

BACKGROUND OF THE INVENTION

The present invention relates, generally, to fluid dispensing assembliesand, more particularly, to electrochemical controlled disposabledispensing assemblies for medicament dispensing.

Fluid or medicament infusion programs are generally preferred to singleor multiple injection programs in that the delivery rate of infusate canbe controlled to a greater degree over a period of time. Typically, theinfusate is topically administered directly onto the skin, wound site oreyes or is injected under the skin or directly into the vascular systemor muscular tissue. In particular, continuous delivery parenteral drugtherapy is most preferred because the controlled delivery of themedicament reduces toxic or other side effects associated with sharppulses of the medicament, significantly improves the effectiveness ofthe therapy program, and increases patient comfort.

Broadly, an infusion device includes a container providing a reservoirof medicament or infusate coupled to a tube having a dispensing channelor the like. The tube includes a dispensing end which communicatesdirectly with the recipient. Disposed in the fluid path between thedispensing end and the reservoir is a regulating device which controlsthe flow rate of the infusate through the channel.

The traditional and simplest infusion device for delivering sustainedparenteral treatments is an intravenous drip apparatus which employsgravity to move the infusate from the reservoir through the channel andinto the patient. The regulating device is often provided by arestrictor in the form of a roller clamp physically acting on anexterior surface of the tube which restricts the flow through thedispensing channel. One problem with these roller clamp restrictors,however, is that they are gravimetrically dependent on the hydrostaticpressure of the infusate formed at the roller clamp. Hence, the rollerclamp cannot accurately regulate the dispensing flow because as thepressure head of the infusate decreases, the hydrostatic pressuredecreases which proportionately reduces the flow rate of the infusatethrough the roller clamp.

To overcome this problem, electronic regulation devices were developedto replace the roller clamp restrictors. These electronic devices arecapable of electronically sensing the flow rate through the channel andautomatically adjusting the restriction area of flow through internaladjusters to maintain the desired infusion rate. While these deviceshave improved the accuracy of intravenous drip apparatus, they areburdensome and impractical since the dispensing reservoir must bepositioned above the recipient at all times to create the properpressure head at the electronic regulation device.

More advanced infusion systems have been developed which actively pumpthe infusate into the patient rather than relying on gravimetricinfusion. Typically, a piston, plunger or the like is urged or advancedinto a fixed volume dispensing reservoir containing the infusate whichpositively displaces the infusate and expels it from the reservoir.Examples of these infusion pumps include syringe pumps, reciprocatingpiston pumps and peristaltic pumps.

The driving forces displacing the piston or plunger are generallyprovided by spring elements, chemical systems or electric resources. Themost common driving force, however, is that provided by an electricmotor which is capable of controlling the infusate flow rate from thedispensing reservoir. Hence, the flow rate of the medicament orpharmaceutical agent suspended in the infusate can be customized to theparticular needs of the patient more accurately than the intravenousdrip apparatus.

While these above-mentioned intravenous drip apparatuses and infusionpumps are perfectly acceptable in a hospital environment, neither areambulatory which severely restricts the activity of the recipient.Hence, considerable research has been devoted to the development ofsmall disposable and portable infusion pumps of the positivedisplacement nature. Electronic powered delivery means or the like wouldprovide a more selectable driving force to control the expulsion of theinfusate from the dispensing reservoir but would not be suitable for adisposable product because of the inherent increased costs and weight.Therefore, these newly developed disposable infusion pumps generallyutilize springs, vapor pressure or elastomeric balloons as a source ofdriving or displacement energy to expel the infusate from the dispensingreservoir.

Due in part to the uncontrolled nature of these sources of drivingenergy, typically, a flow regulation internal restrictor is included inthe fluid flow path between the infusion pump and the dispensing end.These restrictors are generally precision bore tubing elements or filterelements which impede the flow of the infusate through the fluidchannel. Discrete value flow rate restrictors are available toincorporate in the fluid path to selectively establish infusate flowrate. Typical of these portable infusion pumps are disclosed in U.S.Pat. Nos. 4,201,207; 4,318,400; 4,386,929 and 4,597,758.

Presumably, these patented devices provide portability of the infusionpump and provide a range of discrete value restrictors to assure aproper selection of infusate flow rates. In practice, however, the flowrate cannot be precisely selected to suit the needs of a particularpatient. Flow rate of the infusate is dependent on a number of factorssuch as the bore size of the restrictor and the fluid properties of theinfusate. The bulk viscosity, for example, varies from fluid to fluidand is further dependent on the infusate's dispensing temperature.Moreover, infusates containing suspensions often cannot pass through therestrictors because the suspension particles become lodged in the boresor clog the filter elements. Accordingly, a wide range of discrete valuerestrictors as well as an astute knowledge of the infusate fluidproperties must be made available to provide the desired flow rate for aparticular infusate. Due to the economics and logistics, however, onlythe most common discrete value restrictors are produced and made widelyavailable.

Osmotic infusion devices based on the Rose-Nelson pump principle havebeen developed which are activated by imbibition of water (S. Rose andJ. F. Nelson, "A Continuous Long-Term Injector", Austral. J. exp Biol.33, pp. 415-420 (1955)). A Rose-Nelson pump consists of three chambers:a salt chamber containing excess solid salt, an infusate chamber and awater chamber. The salt and water compartments are separated by a rigidsemipermeable membrane permeable to water but impermeable to salt; thesalt and infusate chambers are separated by a elastomeric diaphragm. Aswater is imbibed osmotically into the salt chamber, the salt chamberswells causing the elastomeric diaphragm to expand into the infusatechamber which forces the infusate therefrom through a delivery orifice.Examples of these osmotic infusion devices may be found in U.S. Pat.Nos. 3,604,417; 3,760,984; 3,845,770; 4,193,398; 4,474,575, 4,474,048;4,552,561; and 4,838,862. Generally, the flow rate of the infusate ofthese devices is controlled by osmotic rate controllers which vary oneor a combination of the: osmotic gradient, a function of the salt; thearea of the semipermeable membrane, as well as the membrane's propertycharacteristics.

However, similar to non-osmotic portable and disposable infusion pumpsincluding discrete value internal restrictors, a variety of osmotic ratecontrollers must be available to suit the particular parenteraltreatment needs of the patient. Again, because of economics andlogistics, only the most common flow rates are provided for and madewidely available.

Another form of drug dispensing is that provided by electrochemicallydriven drug dispensers. Generally, a first compartment is providedcontaining electrochemically active fluid molecules (in gas form).Disposed adjacent to the first compartment is a second compartment whichis separated therefrom by an electrolytic membrane. An electrodecontained in the first compartment acts as a catalyst in converting thefluid molecules in the first compartment to ions so that passage throughthe electrolytic membrane is permitted. An opposing electrode containedin the second compartment reconverts or recombines those ions back tofluid molecules in the second compartment. The net result is that fluidfrom the first compartment is recombined in the second compartment tofill the second compartment. The recombined fluid molecules create fluidpressure on an expandable diaphragm separating the second compartmentfrom a drug containing chamber. In turn, the expanding diaphragm expelsthe drug from the chamber. Hence, the fluid pressure is determined bythe magnitude of an electric current applied between the two opposingelectrodes in conductive contact with the membrane and the diffusionrate through the membrane. Typical examples of these trueelectrochemically driven infusion devices may be found in U.S. Pat. Nos.4,687,423 and 4,886,514.

While these devices may provide adequate dispensing of a drug undercertain circumstances, some problems are inherent with these designs. Inorder to electrochemically convert the fluid molecule in the firstcompartment to an ion and then reconvert that ion back to a fluidmolecule on the other side of the electrolytic membrane, a constantcurrent must be applied between the electrodes. Hence, a power source isalways required to provide this sustained current for the duration ofthe dispensing period. Moreover, since the fluid employed to drive thediaphragm is generally gaseous, it is highly susceptible to externalenvironmental changes, such as temperature. Accordingly, the pressureexerted on the diaphragm may vary in these instances and ultimatelychange the rate of dispensing the drug. PG,7

More recently, though still in its infancy, electrochemically controlleddispensing mechanisms for drug delivery have been developed. Theseinfusion pumps, incorporating electrochemical mechanisms, generallyinclude a layered composite of a microporous alumina membrane and a goldmicroporous electrode coated with an impermeable overlay barrier whichspans and covers the micropores of the electrode. On one side of thecomposite is a dispensing reservoir of infusate in flow contact with theelectrode and the barrier which prevents the infusate from flowingthrough the micropores and into a dispensing channel. Hence, by openingthe barrier layer covering the electrode micropores, the infusate ispermitted to pass through the layered composite and into the recipientvia the dispensing channel (M. J. Tierney and C. R. Martin,"Electrorelease Systems Based on Microporous Membranes", J. Electrochem.Soc. Vol. 137, No. 12, pp. 3789-3793 (1990)).

To open this barrier layer, two general techniques are currentlyemployed. The first and more refined technique involves disruption ordissolution of the barrier layer by passing a current through theoverlayer. This dissolvable material layer, preferably a thin metalfoil, is oxidized galvanostatically and dissolved into the infusatesolution, thereby opening the micropores for flow of the infusatetherethrough. The second technique employed to "open" the microporesgenerally involves an overlayer of a polymeric based barrier materialwhich spans the micropores and is impermeable to the infusate. Ingeneral, a gas is generated by electrolysis of the infusate on theelectrode behind the polymer membrane which ruptures the polymermembrane, thereby uncovering the micropores. Because theelectrochemistry is carried out in the medicament or fluid, the infusateis contaminated. Unpredictable chemical reactions or electrochemicalreactions could occur, resulting in toxic products which would beinfused into the recipient. The dispensed drug, for example, could beundesirably modified. Moreover, since the infusate must flow through themicropores of the membrane, the flow rate cannot accurately becontrolled without careful consideration of the infusate fluidproperties (i.e., bulk viscosity), the size of the micropores, and thearea of disruption.

None of the foregoing references is believed to disclose the presentinvention as claimed and is not presumed to be prior art. The referencesare offered for the purpose of background information.

SUMMARY OF THE INVENTION

Accordingly, it is an object of the present invention to provide adispensing assembly and method for dispensing an infusate which can bedelivered at a selective and controlled rate of infusion independent ofthe viscosity or nature of the suspension being infused.

It is another object of the present invention to provide a selective andcontrolled rate dispensing assembly and method for dispensing aninfusate which is electrochemically controlled.

Another object of the present invention is to provide an infusion pumpassembly and method for dispensing an infusate which separates theinfusate from the contaminating electrochemistry.

Yet another object of the present invention is to provide an infusionpump assembly and method for dispensing an infusate which is portable,is complete with drug and pump driving fluid, and can be stored forprolonged periods without deterioration.

It is another object of the present invention to provide a selective andcontrolled rate infusion pump assembly and method for dispensing aninfusate which can be activated quickly and simply.

Still another object of the present invention is to provide an infusionpump assembly and method for dispensing an infusate which automaticallyadjusts to maintain a steady flow rate.

It is a further object of the present invention to provide a selectiveand controlled rate infusion pump assembly and method for dispensing aninfusate which is durable, compact, easy to maintain, has a minimumnumber of components, is easy to use by unskilled personnel, and iseconomical to manufacture.

It is a still further object of the invention to permit a user todeliver a pulse of an infusate when needed or desired. This enables, forexample, patients with certain medical conditions, such as painassociated with bone cancer (PCA--patient controlled analgesia) orpre-term labor control (Terbutylene therapy) to have a steady backgrounddelivery rate and periods of short pulses or boluses of medication toachieve the desired therapeutic effect.

The present invention includes an infusion pump assembly for controlledinfusion of a dispensing fluid. A partition is provided having a frontsurface and an opposite facing back surface, and defines an apertureextending from the front surface to the back surface. On one side of thepartition is a driving fluid reservoir formed for storing a drivingfluid therein which is in communication with the aperture for flow ofthe driving fluid through the partition. A plug member is disposed inthe aperture in a manner preventing flow of the driving fluid throughthe partition. The infusion pump further includes an electric controldevice operably and temporarily coupled to the plug member forcontrolling passage of the driving fluid through the aperture. A barrierdefines a receiving reservoir and is positioned relative to the aperturefor receipt and containment of the driving fluid in the receivingreservoir as the driving fluid flows from the driving fluid reservoirthrough the aperture. The barrier is formed to expand from a firstvolume toward an increased second volume in response to receipt of thedriving fluid in the receiving reservoir. A dispensing reservoir isprovided for holding the dispensing fluid therein and includes anorifice for release of the dispensing fluid therethrough. The barrierseparates the dispensing fluid from the driving fluid, and further ismounted for movement into the dispensing reservoir to communicate withthe dispensing fluid to urge the dispensing fluid through the orifice asthe barrier moves toward the increased second volume. A driving force iscoupled to the driving fluid reservoir for urging the driving fluidthrough the aperture into the receiving reservoir when the electriccontrol device permits passage of the driving fluid therethrough. Theflow of the dispensing fluid can be temporarily increased, such as byusing a one-way pulse pump to deliver a pulse of driving fluid directlyinto the receiving reservoir.

In another aspect of the present invention, a method of controlledinfusion of an infusate is provided comprising the step of: activatingthe electronic control device to effect the opening of the plug memberfor controlling passage of the driving fluid from the driving reservoirthrough the aperture and into the receiving reservoir. Upon receipt ofthe driving fluid in the receiving reservoir, the barrier member expandsfrom a first volume toward an increased second volume causing thedispensing fluid to release through the orifice in the dispensingreservoir.

Accordingly, the present invention provides a disposable electrochemicalcontrolled dispensing assembly having a selectable and controllableinfusion rate.

The invention is especially suited for medical uses. However, theinvention can be applied to other activities where fluids are to bedelivered at near uniform rates over, for example, days or weeks. Forexample, the invention can be used to aid delivery of air fresheners,fertilizers for home plants, sterilants or sanitizers.

BRIEF DESCRIPTION OF THE DRAWINGS

The assembly of the present invention has other objects and features ofadvantage which will be more readily apparent from the followingdescription of the Best Mode of Carrying Out the Invention and theappended claims, when taken in conjunction with the accompanyingdrawing, in which:

FIG. 1A is a front elevation view, in cross-section and partiallydiagrammatic, of a disposable electrochemically driven infusion pumpassembly constructed in accordance with the present inventionillustrating a separating bellows-type barrier in a collapsed condition.

FIG. 1B is a front elevation view, in cross-section and partiallydiagrammatic, of the disposable infusion pump assembly of FIG. 1Aillustrating movement of the separating barrier toward an increased orexpanded condition to expel an infusate from a dispensing chamber.

FIG. 2 is a schematic diagram of one embodiment of the present inventionshowing different sized apertures, provided in a partition member, eachindividually connected to a programming device.

FIG. 3 is an enlarged, fragmentary front elevation view, incross-section, of an individual aperture of the disposable infusion pumpassembly of FIG. 1A employing a dissolvable plug member.

FIG. 4 is an enlarged, fragmentary front elevation view, incross-section, of an individual aperture of the disposable infusion pumpassembly of FIG. 1A employing a switchable gate plug member.

FIG. 5 is a front elevation view, in cross-section and partiallydiagrammatic, of an alternative embodiment of the disposable infusionpump assembly of FIG. 1A and employing an elastomeric diaphragm as aseparating barrier.

FIG. 6 is a front elevation view, in cross-section and partiallydiagrammatic, of an alternative embodiment of the disposable infusionpump assembly of FIG. 1A and incorporating a movable wall as aseparating barrier.

FIG. 7 is a view similar to that of FIG. 1B showing the use of a one-waypulse pump to provide a pulse or bolus of the infusate.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The following description is presented to enable a person skilled in theart to make and use the invention, and is provided in the context of aparticular application and its requirements. Various modifications tothe preferred embodiments will be readily apparent to those skilled inthe art, and the generic principles defined herein may be applied toother embodiments and applications without departing from the spirit andscope of the invention. Thus, the present invention is not intended tobe limited to the embodiments shown, but is to be accorded with thewidest scope consistent with the principles and features disclosedherein. It will be noted here that for a better understanding, likecomponents are designated by like reference numerals throughout thevarious figures.

Attention is now directed to FIG. 1, where the subject disposableinfusion pump assembly, generally designated 20, for selective andcontrolled infusion of a dispensing fluid (infusate) 21 is illustrated.Briefly, the present invention includes a rigid housing or enclosuremember 22 providing an internal cavity. A partition member, generallydesignated 25, extending transverse to a cross-sectional dimension ofthe internal cavity, divides the cavity into a driving reservoir 23 onone side (front surface) 26 of the partition and a dispensing reservoir24 on an opposite side (back surface) 27 of the partition. Partition 25provides at least one aperture 28 extending from front surface 26 toback surface 27. The driving reservoir or chamber is preferablypositioned on the front surface side of partition 25 and is formed forstoring a driving fluid 19 which is in communication with aperture 28for flow of the driving fluid through partition 25. A plug member 30 isdisposed in aperture 28 in a manner preventing flow of driving fluid 19through the partition. The infusion pump further includes electriccontrol means 31 (FIG. 2) operably and temporarily coupled to plugmember 30 for controlling passage of driving fluid 19 through aperture28. A barrier means, generally designated 32, defines a receivingreservoir 33 and is positioned in dispensing reservoir or chamber 24relative to aperture 28 for receipt and containment of received drivingfluid 19' in the receiving reservoir as the driving fluid flows from thedriving reservoir through aperture 28. The barrier is formed to expandfrom a first volume (FIG. 1A) toward an increased second volume (FIG.1B) in response to receipt of driving fluid 19' in receiving reservoir33. The dispensing reservoir contains the dispensing fluid therein andincludes an orifice 34 for release of the dispensing fluid therethrough.Barrier means 32 separates dispensing fluid 21 from the driving fluid,and further is mounted for movement into dispensing reservoir 24 tocommunicate with dispensing fluid 21 to urge the dispensing fluidthrough orifice 34 as barrier means 32 moves toward the increased secondvolume. A driving force means, generally designated 35, communicateswith driving reservoir 23 for urging driving fluid 19 through aperture28 into receiving reservoir 33 when electric control means 31 permitspassage of driving fluid 19 therethrough.

In accordance with the present invention, a disposable infusion pumpassembly 20 is provided which employs electrochemistry to selectivelycontrol the delivery rate of infusate (dispensing fluid) 21 fromdispensing reservoir 24 by selectively controlling the flow rate of thedriving fluid from the driving reservoir to the receiving reservoir. Aswill be described in greater detail below, infusion pump assembly 20includes a disposable infusion pump unit 36 and a separate and remoteprogramming unit 37 (FIG. 2) which forms a portion of electronic controlmeans 31. Initially, once the proper dosage regimen has been prescribed,the separate and remote electronic programming unit can be calibrated toadminister the proper infusate flow rate by selectively controlling thecorresponding flow rate of driving fluid 19. This is accomplished firstby temporarily electrically connecting programming unit 37 anddisposable pump unit 36 together through a port connector 40. Thispermits electronic communication between programming unit 37 and plugmember 30 to control passage of driving fluid 19 through aperture 28.Subsequently, programming unit 37 can be disconnected from disposableinfusion pump unit 36, which acts independently as a medicament infusionpump at the proper selected fixed infusion rate. In one embodiment,after the flow rate has been activated, the present invention onlyoperates as a fixed rate flow infusion pump and can only be turned on oroff using valve means 38. In an alternative embodiment, as will bediscussed in greater detail below, the disposable unit may activelychange the delivery rate of the disposable pumping unit.

The present invention offers several advantages over the priorexperimental electrochemically driven infusion devices and portableinfusion pumps. By effectively employing electrochemistry to control thepassage of driving fluid through aperture 28, the infusate rate can beselectively controlled with a precision unobtainable in the priordisposable infusion pumps. Hence, as will be further detailed below, thedisposable infusion pump of the present invention is capable ofproviding a wide range of infusate flow rates without requiring multipleor combination of multiple parts. Further, barrier means 32 separatesthe electrochemistry in the driving fluid from the infusate so thatcross contamination is eliminated. Moreover, by providing a separate andremote programming unit, the infusate flow rate can be initially set bya physician, medical technician or the like. Patient error and/or abusein the operation of the infusion pump, therefore, is substantiallyreduced. Just as importantly, the more costly electronic components ofelectronic control means 31 can be incorporated with programming unit 37and need not be disposed of when disposable pump unit 36 is no longerneeded. The present invention, further, does not require that a constantcurrent be applied to plug member 30 so as to permit passage of drivingfluid 19 therethrough. Accordingly, it is not necessary for disposablepump unit 36 to include an independent power source. Finally, becausebarrier means 32 separates the driving fluid from the dispensing fluid,a wider range of possible electrochemistries can be utilized as comparedto the experimental models where the electrochemistry was carried outdirectly in the infusate.

In the preferred embodiment of the present invention and as shown inFIG. 1A-2 and 5-6, partition 25 provides a plurality or an array ofindividual apertures 28 each including a plug member 30 which preventsdriving fluid 19 from passage therethrough into receiving reservoir 33.As best viewed in FIG. 2, electronic control means 31 provides that eachplug member 30 is individually addressable through electrical leads 41(FIG. 2) to independently control passage of driving fluid 19 throughrespective apertures 28. Thus, by knowing the fixed geometry of theaperture, the viscosity of the driving fluid and the driving pressureurging the driving fluid through the aperture, an accurate calculationof the driving fluid flow rate through the individual aperture can bedetermined. Accordingly, by activating the passage of driving fluidthrough a discrete and predetermined combination of apertures, thecollective flow rate of the driving fluid can be precisely controlledwhich, in turn, precisely expels the infusate at a controlled flow ratefrom dispensing reservoir 24 through dispensing orifice 34. As viewed inFIG. 2, apertures 28 can be of differing shapes and sizes or may all besimilarly formed (i.e., FIG. 1). Regardless, programming unit 37 will bepreprogrammed or calibrated, as a function of the driving fluidviscosity and driving force, to operate a predetermined combination ofapertures for selective and controlled flow rate of driving fluid 19. Itwill be appreciated, however, that any number and/or combination ofapertures may be provided without departing from the true spirit andnature of the present invention.

Briefly, infusate 21 is preferably a liquid based "drug" or "medicament"solution which denotes any medication composition; in any way affectingany human or animal entity; substance to be assimilated by any humanbeing or animal for its nourishment or for regulating its growth; andsubstance having any other effect on any other environment, especiallyany aqueous environment. Infusate 21 can also be any other fluid whichis to be delivered in a controlled manner, to include fluids used withair freshness, fertilizers for house plants, sterilants and sanitizers.Thus, pump assembly 20 can be used in both medical and non-medicalapplications.

Protective enclosure 22 is preferably a rigid housing constructed ofmaterials that are relatively impervious to invasion by environmentalagents such as oxygen, carbon dioxide, or substances that are derivedfrom components of the device. The internal cavity dimensions ofenclosure 22 will vary according to the desired volume of the drivingreservoir and the dispensing reservoir.

Partition 25 fixedly mounts transversely to the internal cavity andprevents fluid communication between driving reservoir 23 and dispensingreservoir 24, except through apertures 28. In the preferred form,partition 25 is provided by a silicon plate member. The array ofprecision sized apertures or pores 28 are fabricated using siliconmicromachining techniques known in the field. As viewed in FIGS. 2 and3, apertures 28 are preferably obelisk-shaped having side walls inclinedfrom a horizontal of approximately 54.7°. Such precision may befabricated using further known techniques of anisotropic etching.

As previously stated, passage of driving fluid 19 through unblockedapertures 28 is permitted employing electrochemical techniques similarto those described in the M. J. Tierney and C. R. Martin articlementioned above to unblock apertures. In the preferred form, individualplug members 30 are to be formed of an electro-erodible, or dissolvabletype material such as an easily-oxidizable metal film. FIG. 3 bestillustrates that the metal film, such as silver, could be disposed in orgrown across aperture 28 in a manner preventing passage of driving fluid19 therethrough. Preferably, individual metal film plugs are grownacross the aperture proximate back surface 27 by deposition (e.g.,electroplating) onto a sacrificial layer (not shown) which issubsequently removed.

Each metal film plug 30 includes a driving fluid facing surface 42 inflow contact with driving fluid 19, and each is connected to anindividual electrical lead 41 (FIG. 2) in a commonly known manner. Whenleads 41 are temporarily and operably coupled to remote programming unit37 (via port connector 40), each metal film plug 30 essentially forms anindividually addressable electrode in flow contact with driving fluid19. Thus, by providing a large counter electrode 43 or multiple counterelectrodes 43 separate and apart from film plug/electrode 30 and in flowcontact with driving fluid 19, individual electrical circuits can beformed when the driving fluid is an electrolyte. As best viewed in FIG.3, counter electrode 43 is preferably disposed on front surface 26 ofpartition 25 proximate each aperture 28.

When a current, having a sufficient current density, is applied betweena selected metal film plug/electrode 30 and the corresponding counterelectrode 43, the metal film plug/electrode 30 is caused to be quicklyand efficiently galvanostatically oxidized or dissolved into solution.Aperture 28 will then be discretely unblocked (irreversibly) forcontrolled passage of driving fluid therethrough. Accordingly, dependingon the driving fluid viscosity and the driving force acting on thedriving fluid, programming unit 37 can be calibrated to individuallyaddress one or any combination of electrical circuits to oxidize desiredmetal plug/electrodes 30 and produce the desired driving fluid flowrate.

It will be appreciated that due to the uniform thinness of metal filmplug/electrode 30, the plug is quickly and completely dissolved so thataperture 28 is discretely opened for precision flow controltherethrough. Blockage, therefore, of aperture 28 by a partially erodedplug will not occur. It will further be understood that the currentapplied to electrode 30 by programming unit 37 need only be initiallyapplied to dissolve the film plug. Portability of dispensing unit 36,hence, is enhanced since the unit need not carry an independent powersource to permit passage of driving fluid 19 through selected apertures28. It will also be apparent that an Ohm's Law relation can be used tovalidate the complete opening of the apertures

Referring back to FIG. 1A, initially, all apertures are blocked via plugmembers 30. Once plug member 30 or combination of plug members 30 hasbeen dissolved or opened (FIG. 1B), driving fluid 19 (via driving forcemeans 35 discussed below) begins to flow from driving reservoir 23through unblocked aperture 28 for receipt in receiving reservoir 33.Barrier means 32, positioned proximate back surface 27 of partition 25,is of a material impermeable to both driving fluid 19 and infusate 21.Further, the barrier sufficiently surrounds all apertures at backsurface 27 so that all driving fluid 19' passing through the unblockedapertures is received in receiving reservoir 33 and is completelyisolated from infusate 21.

Accordingly, as driving fluid 19 is deposited in receiving reservoir 33,the volume of received driving fluid moves from a first volume (FIG. 1A)toward an increased second volume (FIG. 1B). As best viewed in FIGS. 1Aand 1B, such volume increase positively displaces barrier means 32 intodispensing reservoir 24 which expels infusate 21 therefrom throughdispensing orifice 34 at a preferable one-to-one ratio. The fixed rateof flow of driving fluid 19 through apertures 28 expands the volume ofbarrier 32 toward increased second volume at a constant rate to assureprecision dispensing of infusate 21.

Briefly, dispensing orifice 34 is formed and dimensioned to receive astandard skin-piercing needle or drug delivery set for intravenous use.Alternatively, orifice 34 may receive an apparatus formed to be insertedinto one of the normal body orifices. Orifice 34, when not used in amedical setting, can be formed and dimensioned according to theparticular end use contemplated.

In one preferred embodiment, separating barrier 32 is provided by anexpandable bellows-type barrier (FIG. 1A and 1B) 32 which includespleated walls 44 formed to positively displace into dispensing reservoir24. Therefore, bellow-type barrier 32 must be formed and dimensioned toexpand into dispensing reservoir 24 without interference. An upperperipheral edge portion 45 is formed to completely surround apertures28, and to mount to and cooperate with back surface 27 of partition 25to seal and isolate received driving fluid from dispensing fluid 21.

Alternatively, as viewed in FIG. 5, the barrier means may be provided byan elastomeric diaphragm 32' having a peripheral edge portion 45' whichis also dimensioned to completely surround apertures 28, and to mount toand cooperate with back surface 27 of partition 25 to seal and isolatereceived driving fluid 19' from dispensing fluid 21. Elastomericdiaphragm barrier 32' is further formed to swell or stretch upon receiptof driving fluid 19' in receiving reservoir 33 from the first volume(defined in phantom lines as collapsed diaphragm barrier 32') toward theincreased second volume (defined in solid lines as expanded diaphragmbarrier 32'). Again, receipt of driving fluid expands and moves barrier32' into dispensing reservoir 24 which positively displaces and expelsinfusate 21 therefrom.

A third embodiment of the barrier, illustrated in FIG. 6, is provided bya movable barrier partition 32" or piston member which expels theinfusate from dispensing reservoir as receiving reservoir 33 expandsfrom the first volume (defined by barrier 32" in phantom lines) towardincreased second volume (defined by barrier 32" in solid lines). It willbe appreciated that the movable barrier partition is preferablysubstantially rigid and includes an outer perimeter edge portion 45"formed and dimensioned to slidably cooperate and seal against inner sidewalls 46 forming dispensing reservoir 24. Accordingly, inner side walls46 are preferably substantially perpendicular to back surface 27 ofpartition 25 so that movable barrier partition 32" can slidablycooperate and seal therewith.

It is desirable to utilize driving fluids having the same or similarfluid viscosity which substantially simplifies flow rate calibrations.Moreover, because the same driving fluid medium is flowing through theapertures in all instances, the infusate delivery rate will beindependent of the infusate viscosity which is a problem with most priorart infusion pumps. In the preferred form, isotonic saline solution isprovided as the driving fluid. A saline solution is desirable because ofits efficient electrochemical properties as well as its safeness in useshould the barrier rupture or a leak occur.

As above-mentioned, driving force means or mechanism 35 is communicablycoupled to driving reservoir 23 for urging driving fluid 19 throughselected apertures 28 and into receiving reservoir 33. The pressureexerted on driving fluid 19 by driving force mechanism 35 constitutesone of the factors necessary to accurately determine the driving fluidflow rate. Therefore, it is preferable to maintain a uniform pressure ondriving fluid 19 so that fluid flow is substantially constant.

Driving force mechanism 35 may be provided by a variety of pressuregenerating mechanisms commonly used in other portable infusion pumpassemblies. Preferably, these mechanisms provide a driving force between15-20 psi. Such forms of energy include, but are not limited to:temperature controlled vapor pressure to control pressure; electrolysisof a solution to produce a gas exerting a pressure on the driving fluid;compressed gases; storage of a fluid under pressure in an elastomericcompartment; capillary forces; osmotic pressure caused by the expansionof a volume as fluid permeates through a semipermeable membrane into asalt chamber; and mechanical power sources, such as a compression springelement acting on a movable piston in pressure communication with thedriving fluid. Several of these driving force mechanisms are discussedin greater detail in U.S. Pat. No. 5,135,498.

In the preferred form and as best viewed in FIGS. 1A and 1B, drivingforce mechanism 35 is provided by a constant mechanical driving force 50acting against a movable platform or piston member 51 which causes theplatform to exert a constant pressure on driving fluid 19. Once platform51 moves into driving reservoir 23 and against driving fluid 19, thedriving fluid is positively displaced from the driving reservoir throughthe selected apertures 28 (FIG. 1B). Most preferably, the mechanicaldriving force is provided by a plurality of spaced-apart compressionspring members 50 which generate a balanced low intensity and constantforce against platform 51, biasing it into positive pressure contactwith the driving fluid.

Driving force mechanism 35 may also be provided by expansion of a gasgenerating a driving pressure on driving fluid 19. As shown in FIGS. 5and 6, this may be performed by pressurizing driving reservoir 23. Thisform of driving energy is simple to construct and easy to maintain. Apressure valve or the like (not shown) may be provided so that thepressure can be maintained and/or changed.

In still another alternative embodiment of the present invention, plugmembers 30 may be comprised of a switchable gate membrane 30 capable ofopening, permitting driving fluid 19 to pass through selected apertures28, and closing, preventing passage of fluid 19 through apertures 28.Unlike the above-mentioned electro-erodible or dissolvable plug members,switchable gate membranes can be selectably and reversibly opened andclosed in a manner analogous to a microvalve. This reversiblecapability, hence, not only initiates dispensing of the drug (dispensingfluid 21), but also may stop or reduce flow of the drug. Accordingly,these individually addressable gate elements provide precise control ofthe driving fluid for both a constant or variable rate of flow. As willbe described in greater detail, by opening and/or closing selected gatemembranes 30 at precalculated or preprogrammed times or intervals,complex drug treatment regimens can be administered for optimum drugefficacy.

FIG. 4 illustrates an individual switchable gate membrane 30 disposedtransversely across aperture 28 in a manner preventing flow of drivingfluid 19 therethrough. An individual plug electrode 52 (contrary to thedissolvable plug members 30 where the plug was the electrode) ispreferably positioned against a side wall 53 of aperture 28 and inconductive contact with gate membrane 30 and (although not necessarily)driving fluid 19. Gate membrane 30, therefore, can be individuallyswitched between the opened condition and the closed condition throughprogramming unit 37 via contact with plug electrode 52.

In the preferred embodiment, switchable gate membrane 30 is provided byan electrochemically active polymer membrane having a natural ormanufactured porosity sufficient to permit whole molecules of aqueousdriving fluid to flow through the membrane. As will be described in moredetail below, these electroactive polymers are capable of repelling themolecules of aqueous liquid so that they are unable to pass through thepores. Through electrochemistry initiated by programming unit 37 andplug electrode 52, gate membrane 30 can be selectively changed between apolar (hydrophilic) condition, permeable to driving fluid 19 (preferablyan aqueous electrolyte), and a non-polar (hydrophobic) condition,impermeable to the driving fluid. More specifically, the gate membranepolymers are composed of a material such as Nafion® which is switchablebetween a hydrophilic condition (permeable to water or saline) and ahydrophobic condition (impermeable to water or saline). By modulatingthe hydrophilicity of individually addressable polymer gate membranes,the flow rate of the driving fluid (water) from driving fluid reservoir23 to receiving reservoir 33 can be constantly or variably controlled.

Because barrier member 32 separates and isolates the electrochemistrycontained in the driving fluid from the dispensing fluid, as stated, thesame gate membrane and the same driving fluid may be employed in mostinstances to dispense the drug from dispensing reservoir 24. Thiseliminates the need for tailoring the polymer membrane to the chemicalcharacteristics of the specific medicament or drug to be dispensed.

According to Mark W. Espenscheid et al., "Sensors from Polymer ModifiedElectrodes", J. Chem. Soc., Faraday Trans. 1, 82, 1051 (1986), polymermembrane 30 may comprise a manufactured or naturally porous film capableof passing intact water molecules therethrough. Preferred membranesinclude ionomer films, such as Nafion®. An ionomer is a near or branchedorganic polymer which contains low concentrations of ionizable groupsand which is not covalently cross-linked. Nafion® has been shown topossess a preference for incorporation of large, electroactivehydrophobic cations, such as methyl viologen or a variety of transitionmetal complex cations, such as Ru(NH₃)₆ ³⁺, Ru(bipy)₃ ³⁺, wherebipy=3,2'-dipyridine, and ferrocenylmethyltrimethylammonium, uponelectrochemical treatment. Hence, upon selective ion exchange and theresulting incorporation of a given hydrophobic cation, these ionomermembranes can be modified to repel or reject passage of watertherethrough, thereby preventing the passage of aqueous driving fluidmolecules through the pores of the membrane. In an alternate embodiment,an ionically conductive composite polymer membrane may be utilized, suchas Nafion® impregnated Gore-tex.

Alternatively, electroactive ionomers containing both electroactive andion-exchange functionalities, such as terpolymers based upon styrene,vinylferrocene and styrene sulphonate, may be used. These polymers havebeen shown to reversibly electrorelease incorporated hydrophobiccounterions. More particularly, when the electroactive functionality inthe terpolymer (in this case, vinylferrocene) is in the reduced state,the ion-exchange functionality (styrene sulphonate) requires acounterion, thereby promoting incorporation of hydrophobic cations fromthe surrounding electrolyte solution and altering the electrochemicalcharacteristics of the film so that the resultant modified polymer filmrepels water. Hence, when a counterion, for example, Ru(bipy)₃ ³⁺, isincorporated into the ionomer film, the polymer membrane becomes muchmore hydrophobic (water impermeable) in nature so that the driving fluidcannot flow through the membrane.

Through contact with electrode 52 and upon exposure to an electrolytesolution (i.e., in driving fluid 19), the electroactive functionality inthe ionomer can be oxidized, resulting in an electrorelease or expulsionof the hydrophobic counterion from the film and into the solution. Oncethe counterion is expelled, the electrochemical characteristic of thepolymer membrane is reversibly changed to a hydrophilic state and thewater molecules are permitted to pass through the pores of the membrane.By knowing the flow characteristics of the polymer membrane, the surfacearea of the aperture and the driving force, the flow rate of the drivingfluid therethrough can be calculated and controlled.

Moreover, by reversing the polarity of the polymer membrane (viaelectrode 52), the ionomer film (polymer membrane) can beelectrochemically reduced so that the counterions are drawn from thesolution and reincorporated back into the polymer membrane. Accordingly,by reversing the polarity of the membrane, the hydrophilicity of thepolymer can be modulated in a controlled manner and the apertures can beopened and closed through programming unit 37.

Again, it will be appreciated that the current applied to electrode 52by programming unit 37 to set the polarity of membrane 30 need only beinitially applied. Should the flow rate of the driving fluid need to bechanged subsequently for more complex drug regimens, as will bedescribed below, only a limited duration current is necessary to reversethe polarity of the membrane.

One type of electrochemically active gate polymers are the conductivepolymers which can be selectively electrochemically switched between anelectrically conducting state (hydrophilic or water-permeable) and anelectrically insulating state (hydrophobic or water-impermeable). In theconducting state, gate polymer 30 is generally oxidized and containspositively charged sites on the polymer chain which increase itshydrophilicity. When switched to the insulating state, thehydrophilicity decreases, and the polymer is no longer water-permeable.

Another type of electrochemically active gate polymers are theelectroactive polymers which include side groups that can beelectrochemically oxidized and reduced. Similar to conductive polymers,in an oxidized state, the gate polymer generally contains positivelycharged sites on the polymer chain which increase its hydrophilicity.When switched to the reduced state, the hydrophilicity decreases, andthe polymer is no longer water-permeable.

Once disposable dispensing unit 36 has been temporarily electricallycoupled to programming unit 37 (via connector 40) the dosage regimen canbe initially set by operating programming unit 37. Depending on thecorresponding flow rate, programming unit 37 will automatically select aparticular one or predetermined combination of plug members 30 tooxidize or dissolve into the driving fluid solution (taking intoconsideration the driving pressure and driving fluid viscosity)discretely opening the corresponding aperture.

Driving force mechanism 35 may include an activation device 54, as shownin FIGS. 5 and 6, which permits the pressure exerted by the drivingforce mechanism to act on driving fluid 19 contained in the drivingreservoir. Device 54 may be provided by a simple manually operable valveor may include an electronic switch. Similarly, as a further precaution,drug delivery may begin or be stopped upon opening or closing manualvalve 38 at orifice 34.

When the flow rate has been programmed and activated, the disposablepump unit can be disconnected from programming unit 37. In oneembodiment of the present invention, pump unit 36 operates only as afixed rate unit and can only be turned on or off using manual valve 38.A second microprocessor (not shown), incorporated in disposable unit 36,may be coupled to driving mechanism 35 which is capable ofmicro-adjustments to maintain a more constant driving force.

In other embodiments, the dosage regimen may be varied by changing thedriving fluid flow rate. To simply increase the flow rate, thedisposable pump unit may be temporarily reconnected to the programmingunit where additional apertures may be unblocked. More complexapplications may include varying the force exerted on the driving fluidfrom the driving force mechanism. Driving force means 35, for example,may include pressure adjusting means 55 which controls the pressureexerted on driving fluid 19. Pressure adjusting means 55, may beprovided by a pressure intake/exhaust valve or a valve capable of flowcontrol. For a more detailed description of various pressure adjustingmechanisms, Athayde et al., U.S. patent application Ser. No. 07/503,719,is hereby incorporated by reference.

Furthermore, when employing switchable gate membranes 30, as statedabove, selected gate membranes 30 may be opened and/or closed atprecalculated or preprogrammed times or intervals so that complex drugtreatment regimens can be administered for optimum drug efficacy. Forexample, disposable unit 36 may include a regimen microprocessor whichis programmed (via programming unit 37) when disposable unit 36 isinitially coupled to programming unit 37. The regimen microprocessor maystore a set of commands which activate certain combinations of gatemembranes 30 at predetermined times or intervals for flow rate controlof the driving fluid. Moreover, since only a limited duration current isnecessary to reverse the polarity of the membrane, only a very smallpower source needs to be incorporated in disposable unit 36.Accordingly, this embodiment permits more complex and preciselyadministered regimens from a portable dispensing unit.

Another embodiment of the present invention employing switchable gatemembranes may include patient activated boluses, as used in painmanagement, where the patient may self administer the drug. In thisembodiment, a manually operable switch electrically coupled to theregiment microprocessor may be self activated to administerprecalculated (i.e., through programming unit 37) or limited quantitiesof drug within a predetermined time span.

FIG. 7 illustrates a further alternative embodiment of the invention,similar to the embodiment of FIGS. 1-3, but modified to permit adifferent form of patient-activated, or other user-activated pulses orboluses of infusate 21. Pump unit 36 includes a one-way, user-activatedpulse pump 60 coupled to an intake line 62 at its inlet 64 and an outletline 66 at its outlet 68. Intake line 62 passes through platform 51 andopens into driving reservoir 23. Outlet line 66 passes through platform51 and partition 25 and opens into receiving reservoir 33. Actuatingpump 60 causes a pulse or bolus of driving fluid 19 to pass through line62, pump 60, line 66 and into reservoir 33. This causes a correspondingpulse or bolus of infusate to be delivered through orifice 34 to, forexample, a patient. To prevent over medication, actuation of pump 60 canbe limited or controlled by a pulse frequency limiter 70 which acts tolock out pump 60 for, typically, a pre-set time period after pump 60 hasbeen actuated. Pump 60 could be mechanically or electrically actuated.Intake line 62 could be coupled to a separate reservoir of driving fluid19 instead of driving reservoir 23.

The disposable infusion pump unit of the present invention can beattached to the body of the wearer by means of a biocompatible adhesivecoating on the base of the assembly, or by adhesive strips or overlays,and does not mandate the use of straps, belts, or other carryinggarments. The device may be attached anywhere on the body that isconvenient, either immediately adjacent to the delivery site, or at apoint from that site.

Particularly when describing the source of the driving force of thisinvention, embodiments will employ components that are dependent on theresistance forces of the pump, the driving fluid employed, the infusatebeing delivered, and other variables. The choice of components used inthe various foregoing general descriptions and the following detaileddescriptions are exemplary and explanatory, but are not restrictive ofthe invention.

Because the devices described in the present invention are small andsimple, they are particularly suitable for delivering small infusatevolumes. The disposable pump unit of this invention, while it can betailored for a range of infusate volumes and dosage rates, isparticularly useful where the total infusate volume to be dispensed isof the order of one to 50 milliliters, and the delivery time for thatvolume is one hour to seven days. Thus, the invention enables therapyinvolving highly potent substances, such as peptide drugs of variouskinds, heparin and insulin, analgesics and anesthetics, corticosteroids,immunosuppressants, antineoplastics, antibacterials, and antidotes tochemical or biological poisons and the like, to be administered withoutsubjecting the patient to repeated injections or requiring the patientto be attached to an intravenous drip.

In another aspect of the present invention, a method of controlledinfusion of an infusate is provided comprising the step of: activatingelectronic control device 31 to effect the opening of plug member 28 forcontrolling passage of driving fluid 19 from driving reservoir 23through aperture 28 and into receiving reservoir 33. Upon receipt of thedriving fluid in the receiving reservoir, barrier member 32 expands froma first volume toward an increased second volume causing dispensingfluid 21 to release through orifice 34 in the dispensing reservoir.

Other modifications and variations can be made to the disclosedembodiments without departing from the subject of the invention asdefined by the following claims.

What is claimed is:
 1. A pump assembly for controlled delivery of adispensing fluid comprising:a partition having a front surface and anopposite facing back surface, and defining an aperture extending fromsaid front surface to said back surface; a driving reservoir formed forstoring a driving fluid therein and in communication with said aperturefor flow of said driving fluid through said partition; plug meansdisposed in said aperture in a manner preventing flow of said drivingfluid through said partition; electric control means operably coupled tosaid plug means for controlling passage of said driving fluid throughsaid aperture; barrier means defining a receiving reservoir andpositioned relative to said aperture for receipt and containment of saiddriving fluid in said receiving reservoir as said driving fluid flowsfrom said driving reservoir through said aperture, said barrier meansseparating said dispensing fluid and said driving fluid, and furtherformed to expand from a first volume toward an increased second volumein response to receipt of said driving fluid in said receivingreservoir; a dispensing reservoir for holding said dispensing fluidtherein, said dispensing reservoir defining an orifice for release ofsaid dispensing fluid therethrough, said barrier means being mounted formovement in said dispensing reservoir in a manner communicating withsaid dispensing fluid to urge said dispensing fluid through said orificeas said barrier means moves toward said increased second volume; andmeans for temporarily increasing the flow of the driving fluid to thereceiving reservoir so as to deliver a temporarily increased flow of thedispensing fluid through the orifice.
 2. The pump assembly of claim 1wherein the temporarily increasing flow means further comprises meansfor delivering a pulse of the driving fluid from the driving reservoirto the receiving reservoir so to deliver a pulse of the dispensing fluidthrough said orifice.
 3. The pump assembly of claim 2 wherein thedriving fluid pulse delivering means is a user-actuated means.
 4. Thepump assembly of claim 3 wherein the driving fluid pulse deliveringmeans includes means for limiting the frequency of actuation thereof.